Using biophysical methods and chemical biology to explore function and design in the tandem-repeat protein class

布景主题：世界级的基础生物科学我们的研究重点是一类蛋白质，称为串联重复蛋白，具有非常独特的结构（例如锚蛋白，tetratricopeptide和armadillo repeats）。这些蛋白质在人类疾病中经常被失调，例如癌症和呼吸道和心血管疾病。重复蛋白的各个模块以线性方式堆叠以产生高度伸长的超螺旋结构，从而呈现用于分子识别的延伸支架。术语“支架”意味着一种刚性的结构;然而，正如其弹簧状形状所暗示的那样，人们认为重复阵列利用了更多的动态和弹性作用模式。重复序列蛋白简单的模块化结构使它们能够独特地解剖其生物物理特性以及合理地重新设计这些特性。博士项目将继续从轮换项目的目标嫁接到重复蛋白质支架的新功能。关键技术将是蛋白质工程，生物物理分析和X射线晶体学。细胞生物学将用于测试设计的蛋白质及其功能。我们也在考虑与Luca Pellegrini博士（生物化学系）的合作项目。ENWW将主要涉及实验数据的统计分析。为此，将使用R等统计工具。

Theme: World-Class Underpinning BioscienceThe major focus of our research is a class of proteins, known as tandem-repeat proteins, with very distinctive architecture (e.g. ankyrin, tetratricopeptide and armadillo repeats). These proteins are frequently deregulated in human diseases such as cancers and respiratory and cardiovascular diseases. The individual modules of repeat proteins stack in a linear fashion to produce highly elongated, superhelical structures, thereby presenting an extended scaffold for molecular recognition. The term 'scaffold' implies a rigid architecture; however, as suggested by their Slinky spring-like shapes, it is thought that repeat arrays utilise much more dynamic and elastic modes of action. The simple modular architecture of repeat proteins makes them uniquely amenable to the dissection of their biophysical properties as well as the rational redesign of these properties. The PhD project will continue from the rotation project with the goals of grafting new functions into repeat-protein scaffolds. Key techniques will be protein engineering, biophysical analysis and X-ray crystallography. Cell biology will be used to test the designed proteins and their function. We are also thinking about a collaborative project with Dr. Luca Pellegrini (Department of Biochemistry).ENWW will mainly involve statistical analysis of experimental data. For this purpose, statistical tools, such as R, will be used.